This application presents a research plan for the renewal of R01 DA 13004 "Opioids and HIV Medications- Interactions in Drug Abusers". The overall objective of this work is to improve the clinical care of human immunodeficiency virus (HlV)-infected, substance-abusing patients by identifying significant interactions that occur between drugs commonly used to treat HIV disease and opioid therapies used in treatment of opioid dependence. The currently funded project has identified drug interactions of clinical importance between opioid therapies and HIV medications (nelfinavir, ritonavir, lopinavir/ritonavir, efavirenz and delavirdine).The proposed project will continue a series of drug interaction studies with buprenorphine, the newest opioid used for maintenance treatment of opioid dependence and antiretroviral medications frequently used in HAART regimens. The study design is a cost-effective method for rapid determination of the presence and of the clinical significance of drug interactions between buprenorphine and antiretroviral therapies. The project includes a within-subject component in which buprenorphine plasma concentrations are determined prior to and following antiretroviral administration to reveal whether the pharmacokinetics of buprenorphine are altered by co administration of any of the following HIV medications: nevirapine, atazanavir, atazanavir/ritonavir, fosamprenavir, fosamprenavir/ritonavir, tenofovir, or didanosine. Antiretroviral medication pharmacokinetics alone and in the presence of buprenorphine will be determined using a between-subjects study design and will elucidate the presence and significance of buprenorphine effects on the HIV therapeutics of study. Drug interaction studies of the type proposed have been identified as a priority research area for NIDA because of their importance to optimizing the clinical care of HIV disease in opioid dependent patients.